Clinico-prognostic relevance of quantitative immunophenotyping in B-cell chronic lymphocytic leukemia with emphasis on the expression of CD20 antigen and surface immunoglobulins.
Expression of CD20, evaluated as antibody binding capacity (ABC) (i.e. absolute number of molecules of antibody per cell), was analyzed using flow cytometry on leukemic cells of 93 previously untreated patients, all fulfilling strict criteria of "immunologically typical" (i.e. CD5+, CD23+) B-cell chronic lymphocytic leukemia (CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04). Given the correlation between CD20 ABC and mean fluorescence intensity (MFI) of light chain (LC) surface immunoglobulins (Sm Ig) (r = 0.481, p < 0.0001), as well as the impact of MFI of Sm Ig LC on overall survival (p = 0.01; relative risk of death 0.44; 95% confidence interval, 0.10 to 0.76), we tried to verify whether a combination of B-cell markers, evaluated in a quantitative manner, could have additive prognostic properties. To this purpose we gave a value of 1 or 0 to each B-cell marker according to whether it was expressed at a low (i.e. CD20 ABC < 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig < 100) or high (i.e. CD20 ABC > or = 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig > or = 100) level thus allowing patient stratification into two groups with scores of 2 and 0-1, respectively. Survival of patients who scored 2 was significantly longer respectively. Survival of patients who scored 2 was significantly longer than that of patients who scored 0-1 (p = 0.02; relative risk of death, 0.44; 95% confidence interval, 0.22-0.72). However, when quantitative changes of CD20 antigen and LC Sm Ig expression, either alone or in combination, were simultaneously analyzed in a Cox model which included usual clinico-hematological features, only absolute peripheral blood lymphocytosis (p = 0.0001) and Binet clinical stages (p = 0.0001) maintained their prognostic power unmodified. Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients.
Molica
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S
Divisione Ematologia, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.
Levato
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D
Dattilo
A
A
Mannella
A
A
D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000032:analysis*; D018956:CD5 Antigens / Q000032:analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D017455:Receptors, IgE / Q000032:analysis
D018951:Antigens, CD20; D018956:CD5 Antigens; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE